Fast axonal transport is of critical importance to neuronal development since it is the means by which proteins required for synaptic function are delivered to the nerve terminal. Sensory and motor neurons of the developing hindlimbs of bullfrog tadpoles are an excellent system for studies on the functional role of fast transport since (i) the time courses of such events as axon elongation, myelination, synapse formation and synapse elimination have been well-studied during metamorphosis; and (ii) thyroid hormones, that are known to regulate metamorphosis in tadpoles, have been shown to affect differentiation of nerve and muscle. We propose, first, to identify changes in amount, composition and destination of fast-transported proteins that correlate temporally with known events in neuronal development, and second, to determine the extent to which changes in fast transport are controlled by thyroid hormones. Aspects of fast transport that will be examined during periods of axon growth and synaptic development of dorsal root ganglion neurons and spinal motor neurons include (i) quantitative and qualitative changes in individual fast-transported proteins; (ii) changes in glycosylation and sulfation of fast-transported proteins; (iii) changes in the proportions of fast-transported proteins destined for nerve terminal as opposed to axolemma; (iv) changes in the proportions of fast-transported proteins destined for secretion as opposed to membrane insertion; and (v) changes in fast transport rate. The second major series of experiments will explore effects of triiodothyronine (T3) and thyroxine (T4) on fast transport in both sensory and motor neurons. Since in vivo administration of T3 or T4 (by injection or immersion of tadpole in hormone) accelerates metamorphosis, we will examine effects on fast transport of pretreating premetamorphic tadpoles with hormone. The developmental period during which neurons are sensitive to the hormones will be determined. In addition, we will investigate whether thyroid hormone-related changes in fast transport can be mimicked by in vitro administration of hormones. This approach will enable us to explore the subcellular site(s), e.g. soma vs. axon, at which the hormones affect transport, and to use pharmacological agents to test recent findings that the hormones act at sites in addition to those at the cell nucleus, e.g. on plasma membrane-bound cAMP systems.